Antidiabetic Drugs Linked to Reduced Asthma Attacks: Study Highlights Synergistic Benefits of Metformin and GLP-1RA

"Metformin was linked to a notable reduction in asthma attacks, and the addition of GLP-1RAs, a newer class of drugs used to treat diabetes, produced a synergistic, additive effect," the researchers wrote.

Asthma, a chronic respiratory condition characterized by inflammation and narrowing of the airways, has been linked to various factors, including genetic predisposition, environmental triggers, and comorbid conditions like obesity and diabetes. High body mass index (BMI) and type 2 diabetes are common in people with asthma and can increase the risk of asthma attacks. Experimental studies show that diabetes medications like metformin and glucagon-like peptide-1 receptor agonists (GLP-1RAs) may help reduce airway inflammation and other asthma symptoms. However, there is limited epidemiological evidence to support these findings.

To fill this knowledge gap, Bohee Lee, National Heart and Lung Institute, Imperial College London, London, England, and colleagues aimed to evaluate the relationship between metformin and additional anti-diabetic medications (such as GLP-1RAs, sulfonylureas, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, and insulin) and the occurrence of asthma attacks.

For this purpose, the researchers used data from the UK Clinical Practice Research Datalink (CPRD) Aurum, linked with hospital admissions and mortality data from 2004 to 2020. They applied a triangulation approach using two methods: a self-controlled case series (SCCS) and a metformin new user cohort with inverse probability of treatment weighting (IPTW).

The study focused on new metformin users with type 2 diabetes. The primary exposure was metformin, with secondary exposures being other antidiabetic medications. The primary outcome was the first asthma exacerbation during a 12-month follow-up, assessed using incidence rate ratios and hazard ratios.

Key Findings:

• The study included 4278 asthma patients (2617 women, 61.2%; mean age 52.9 years) for the SCCS analysis and 8424 patients (4690 women, 55.7%; unexposed mean age 61.6 years, exposed mean age 59.7 years) for the IPTW cohort.
• Metformin use was associated with fewer asthma attacks in both analyses (SCCS: IRR 0.68; IPTW: HR 0.76).
• Negative control analyses showed no significant bias.
• The association was not modified by hemoglobin A1c levels, BMI, blood eosinophil counts, or asthma severity.
• The only add-on antidiabetic medication with an additive effect was GLP-1RA (SCCS: IRR 0.60).

"The cohort study indicates that metformin use was linked to a reduced rate of asthma attacks, with additional reductions observed when combined with GLP-1RA. These effects appeared independent of glycemic control or weight loss and were consistent across various asthma phenotypes," the researchers concluded.

Reference:

Lee B, Man KKC, Wong E, Tan T, Sheikh A, Bloom CI. Antidiabetic Medication and Asthma Attacks. JAMA Intern Med. Published online November 18, 2024. doi:10.1001/jamainternmed.2024.5982